Abstract
Background: Considering that the therapeutic function of adipose tissue-derived mesenchymal stem cells (ADSCs) on skin wounds is closely related to their paracrine effect, this study was designed to investigate the therapeutic effect of ADSC conditioned medium (ACM) on type 2 diabetic (T2D) skin wound healing.
Methods: The effect of ACM on HUVEC viability and angiogenesis was firstly evaluated by CCK 8 assay and q-PCR analysis, respectively. Next, a T2D rat model was induced by the combination of high fat diet and streptozotocin. Following by the establishment of full-thickness skin defects in T2D rats, ACM or serum free cultured medium was daily injected around the wound edge sfor 7 days. Afterwards, the skin wound healing rate was analyzed, and the skin tissues were assessed by histopathological examination. The mRNA levels of TNF-α, IL-1β, IL-6, and COX-2, as well as IL-12 and IFN-γ were evaluated by q-PCR analysis. Additionally, the transcriptome sequencing and immunohistochemistry were used to reveal the potential mechanism of ACM for T2D skin wound healing.
Results: Our data showed that ACM promoted cell proliferation and angiogenesis, and up-regulated the mRNA expression of EGF, bFGF, VEGF, and KDR in HUVECs. The in vivo data indicated that ACM could accelerate T2D skin wound healing rate by inhibiting the mRNA levels of TNF-α, IL-1β, IL-6, and COX-2, as well as IL-12 and IFN-γ in vivo. Particularly, we also found that ACM could down-regulate TNF and chemokine signaling.
Conclusions: ACM could effectively promote vascular cell angiogenesis, accelerate skin wound regeneration by suppressing excessive inflammation in T2D rats, which is closely related to down-regulation of TNF and chemokine signaling pathways.